The present invention relates to a novel process for preparation of an optically active 1-halogeno-2-hydroxypropyl compound and an optically active glycidyl compound useful as an intermediate for synthesis of medicines or agrochemicals.
The preparation methods for a glycidyl compound via a 1-halogeno-2-hydroxypropyl compound were reported in many documents from of old.
However, most of the methods relate to a process for preparation of a racemic glycidyl compound starting from a racemic epihalohydrin. The preparation methods for an optically active gycidyl compound starting from an optically active epihalohydrin were not reported in plenty. One of the reasons is because there is no significant difference in activity between the active positions on epihalohydrin, namely halogenomethylene at position 1 and the terminal position on epoxy ring at position 3 and therefore, it is not easy to handle it. Namely, as shown in the following reaction scheme, in reaction with a nucleophilic substance, it is considered that nucleophilic reaction shown by route a theoretically precedes to give a compound [I] or [II], but practically, thus specificity or selectivity is not complete and therefore, the reaction shown by route b also occurs to give a compound [III] in small amount as a side product. As a result, optical purity of the object compound [II] decreases. 
wherein X′ is halogen atom and Nu′ is a residue of nucleophilic substance.
In order to solve the above problem, several methods were developed, such as (i) a method for reacting an optically active epihalohydrin and 4-carbamoylmethylphenol in the presence of an alkali hydroxide and a quaternary ammonium salt in an aqueous solvent (Japanese Patent Publication B 6-374823, and (ii) a method for reacting an optically active epihalohydrin and benzylalcohol in the presence of boron trifluoride-diethyl ether (Heterocycles, 31, 1715 (1990)), but in any case, optical purity of the glycidyl compound obtained is 1-2% lower comparing with one of the epihalohydrin used for a starting material. Therefore, the improvement of the process of preparation for an optically active glycidyl compound is still desired.
On the other hand, according to a method for treating with potassium carbonate after the reaction with an optically active epichlorohydrin and water in the presence of an optically active cobalt (III) complex (J. Am. Chem. Soc. 124, 1307 (2002)), an optically active glycidol is obtainable in highly optical purity. However, in case of carrying out this reaction, an optically active cobalt (III) having a specific steric configuration have to be made and to be used according to each configuration of the epihalohydrin used as a starting material. Therefore, this method is troublesome and not economical.